The role of cyclic nucleotides in lymphocyte transformation. In continuance of prior studies it was found the cyclic AMP inhibited stimulus of lymphocytes by pokeweed mitogen and concanavalin A as well as by PHA. Levels of cyclic AMP therefore appear to exert a regulatory influence in the proliferation of both B and T lymphocytes. A deficiency of the enzyme adenosine deaminase (ADA) has been reported in several families to be associated with a syndrome of severe combined immunological deficiency. It is not clear if the deficiency of the enzyme is causally related to the immunological disorder or represents a fortuitous association resulting from some other event such as chromosome deletion, involving both the locus for ADA and for "immune differentiation genes". In studies of ADA during lymphocyte stimulation by PHA a disappearance of one of the isozymes of ADA has been found. This may represent the loss of a regulatory isozyme. In studies of tissue from one of the original cases reported, absence of all of the isozymes of ADA has been found. This would indicate that a single gene controls at least a subunit common to all of the different tissue specific isozymes of ADA. In confirmation of this finding, a conversion factor has been shown to be present in the tissue of this child as well as normal. This can convert the polymorphic red blood cell ADA to the tissue specific isozyme.